Polycystic Kidney Disease Causes and Treatment

Polycystic Kidney Disease Causes and Treatment   Introduction: Polycystic kidney disease effects roughly 10 million people worldwide. Even though this disease is so prominent it lacks research in the field of therapeutics from biopharmaceutical companies as they invest their resources into fields which are seen to be more profitable i.e. cancer research. This lack of research is what enticed us to carry out our project on polycystic kidney disease. This project will firstly outline the history of the polycystic kidney disease, how it effects patients, the cause of the disease and the current therapeutic treatment available to combat polycystic kidney disease in section 1. Section 2 will look at the current diagnostic methods employed by a physician to see if a patient is suffering from polycystic kidney disease. Diagnostic methods such as imaging and genetic testing will be dealt with here. Lastly section 3 will look at a potential new diagnostic technique which has been formed using proteomic techniques to identify the difference between a healthy polycystin-1 protein compared to a mutated polycystin-1 protein. The first record of Polycystic Kidney Disease (PKD) is from the 16th century. In 1586, the King of Poland died from cysts on his kidneys. The cysts were described by his surgeon as large like those of a bull, with an uneven and bumpy surface. At the time of his death he was diagnosed with meningeal abscesses. It wasnt until a group of physicians re-examined the records of the Kings death over 300 hundred years later that his cause of death was agreed to be PKD. The term polycystic kidney disease was first used by Fà ©lix Lejars in 1888, although the mode of inheritance of this disease wasnt understood for almost another one hundred years. In the 1990s, the formation of cysts was understood at a molecular level. This helped in the discovery of the genes that cause PKD (Ayse, 2016). Figure.1 A visual representation of the transmembrane proteins Polycystin-1 and Polycystin-2. Also seen is the Polycystin-1 receptor located in extracellularly. (Gallagher, Germino and Somlo, 2010) PKD is a genetic disease in which the renal tissue within the outer cortex and inner medulla is replaced with fluid filled sacs (or cysts). These cysts enlarge the kidneys and inhibit kidney function. Hypertension, hematuria and chronic pain are the most common symptoms associated with PKD (Seeger-Nukpezah et al., 2015). PKD has two forms; Autosomal Dominant (ADPKD) and Autosomal Recessive (ARPKD). ADPKD is the result of the inheritance of one mutant PKD1 or PKD2 gene, which affects ~1:750 people worldwide. 85% of ADPKD cases are caused by mutations in PKD1. Mutations in this gene lead to earlier disease onset. The other 15% of cases are attributed to a mutation in PKD2. All ADPKD patients inherit one normal allele and one mutant allele. Cases where both alleles have the dominant mutation lead to embryonic lethality. ARPKD is caused by the inheritance of two recessive mutated PKHD1 genes. ARPKD is considerably less common with an incidence of 1:20,000. ARPKD progresses at a much faster rate than ADPKD. It usually causes death at birth or requires transplantation in early childhood. Multiple different types of mutations in PKD1, PKD2, and PKHD1 have been researched, including frameshifts, deletions, and premature stop codon insertions (Wilson, 2015). In the dominant form of PKD there is only one mutated gene inherited. This mutated gene is unable to produce the proteins PC-1 or PC-2. However, the non-mutated allele can still function as normal and can produce enough of the polycystin proteins to maintain kidney function. It is only when a somatic mutation occurs causing the normal allele to become inactivated that symptoms of the disease will occur. (Torres and Harris, 2010) PKD-1 is located on the short arm of chromosome 16 (16p13.3). PKD-2 gene is located on the long arm of chromosome 4 (4q21) (Nowak et al., 2016). Polycystin-1 and 2 are large transmembrane proteins which are encoded by PKD1 and 2. Both proteins affect multiple downstream signalling proteins (Seeger-Nukpezah et al., 2015). In a normally functioning nephron as the urinary filtrate flows by and causes the primary cilia to bend polycystin 1 and 2 respond by allowing calcium influx which activate pathways in the cell which inhibit cell proliferation. PC1 has the ability to sense when the primary cilia bends which activates PC2 calcium channels. If either PC1 or PC2 is absent the signal to inhibit cell growth is not received (Chebib et al., 2015). PKD1 or PKD2 mutations cause a reduction in intracellular calcium. This triggers a change in the response of the cell to cyclic adenosine monophosphate (cAMP) from suppression to proliferation. The concentration of cAMP directly affects the activity of Protein Kinase A. Four cAMP molecules are required to activate one PKA enzyme. The increased production of cAMP via adenylyl cyclase 6 is dependent on vasopressin (Chebib et al., 2015). Despite the many breakthroughs in research allowing for a greater understanding of the disease, there is currently no cure for PKD. However, there are drugs which can suppress symptoms brought on by the disease. Beta blockers such as, Tenormin, can be used to treat hypertension and haematuria can be treated with antibiotics. Understanding the effect of PC1 and PC2 mutations on the vasopressin receptor in the cell lead to the development of Tolvaptan. This drug slows down the formation of cysts in the kidneys. Tolvaptan blocks the vasopressin receptor, which will stop the signalling pathway. Therefore, cAMP production will be reduced. (Ema.europa.eu, 2017) The current diagnostic methods for polycystic kidney disease include genetic testing, pre-natal testing and imaging studies in the form of ultrasounds, CT (Computed Tomography) scans and MRI (Magnetic Resonance Imaging) scans The imaging studies take a scan of the kidneys to identify the presence of any abnormalities in the form of renal cysts. An ultrasound mechanism uses high frequency sound waves to capture and visualise images that cant be seen with the naked eye. The CT scan combines many x-ray images with the aid of a computer to generate cross sectional views and/or three-dimensional images of the kidneys and the MRI scan uses a magnetic field and pulses of radio wave energy to from pictures of the kidneys. The appearance of three or more renal cysts, either unilateral or bilateral, on the image is enough to diagnose a patient between the ages of 15 and 39 with polycystic kidney disease. In patients aged 40 59, the presence of two or more cysts in each kidney fulfils the criteria to diagnose the patient with polycystic kidney disease. The presence of four or more cysts in each kidney is used to diagnose older patients (F. Belibi et al., 2008). The kidneys on an image may appear enlarged but retain their normal reniform shape in the case of a patient presenting with possible polycystic kidney disease. The medullary pyramids in the centre of the kidney may be more visible on an image in contrast to the cortex which can give a peripheral halo on the image obtained. High resolution imaging studies allows the visualisation of numerous cylindrical cysts within the medulla and the cortex which represent ectatic collecting ducts within the kidney (F. Gaillard, 2015). Genetic testing for polycystic kidney disease is for those who have a family history of polycystic kidney disease who has no symptoms and may consider being screened for the disease. Genetic tests can be done to screen for both PKD1 or PKD2 mutations. A method of PCR known as PCR- SSCP (Polymerase Chain Reaction Single Strand Conformation Polymorphism) is used to view mutations, if any, in the patients genomic DNA. In SSCP analysis, a mutated DNA sequence is detected as a change of mobility in polyacrylamide gel electrophoresis caused by the altered folded structure of single-stranded DNA (K. Hayashi, 1991). The genomic DNA of the white blood cells in patients with the possible polycystic kidney disease gene are isolated. These samples of genomic DNA are then amplified by PCR using two primers to amplify the potential polycystic kidney disease genes (R. Jas et al., 2012) The PCR product is then analysed using the SSCP method. This method involves loading the PCR product samples onto the acryl amide gel and gel electrophoresis occurs. After completion of the gel electrophoresis step, the gel is subjected to silver staining to visualise the SSCP band patterns (B. Yadav et al., 2009). The silver stained gel is kept on a transilluminator and the SSCP variants are recorded. DNA samples from the abnormal bands seen on the transilluminator are sequenced to see what kind of mutation and where the location of the mutation is on the polycystic kidney disease gene (Z. Dian-Yong et al., 2002). In PCR-SSCP analysis, changes in several hundred base pairs are detected in contrast with other techniques in which changes in relatively short sequences can be detected. Because of this, PCR-SSCP analysis is much more sensitive to the replication errors that can occur during the PCR process (K. Hayashi, 1991). Diagnosis of polycystic kidney disease can also be done prenatally. If the parents agree, a prenatal diagnosis can be done on the developing fetus if there is a history of polycystic kidney disease in either the parents or extended family . A DNA sample is taken from both parents and a sample of tissue is taken from the fetus. The tissue sample is obtained from the fetus by a procedure called aminocentesis which involves passing a needle into the mothers lower abdomen and into the amniotic cavity inside the uterus. The sample is then amplified by PCR to detect any mutations in the DNA that could lead to the fetus developing polycystic kidney disease in the future (K. MacDermot et al., 1998). The imaging studies, genetic testing and prenatal testing for polycystic kidney disease have advantages and disadvantages. One advantage of the imaging studies is that they are reliable, inexpensive and a non-invasive way to diagnose polycystic kidney disease (A.Khan, 2015). A disadvantage of imaging studies is that while they are sensitive in the detection of polycystic kidney disease, problems may arise with smaller cysts. Smaller cysts on scans may not be easily differentiated from small, solid masses within the kidneys (A.Khan, 2015). An advantage of CT scans when compared to MRI scans is that the cysts on the kidney will enhance on the image when dye is administered into the patient intravenously (A. Khan, 2015) (F. Gaillard, 2015). MRI scans of the kidneys are becoming a useful technique in diagnosing more complicated cysts and can be used in addition to or instead of CT scans (A. Khan, 2015). The advantage of genetic testing as a method of diagnosing polycystic kidney disease is that it can determine if a person who has a relative with polycystic kidney disease will in the future start showing symptoms of the disease. Some disadvantages of genetic testing as a method of diagnosing polycystic kidney disease is that they are extremely costly tests to carry out and sometimes they cant pick up on certain gene mutations that could eventually lead to the person having polycystic kidney disease (National Kidney Foundation, 2016). The major advantage of prenatal testing for polycystic kidney disease is the fact that treatment using cyst suppressing drugs can be used early in the diseased patients life meaning the formation of renal damaging cysts will be slowed down drastically compared to a patient who was not on the cyst supressing treatment early in their life time. The negative of prenatal testing is of course the invasive nature of extracting tissue from the foetus which many parents would not agree with however the benefits of early diagnosis of this disease will lead to a better quality of life for the child in their later years. As discussed in the previous section the current diagnostic methods for diagnosing polycystic kidney disease is through the use of various scans and genetic testing. The genetic testing is carried out by analysing the DNA sequence in order to identify any mutations which may be present. As a new method of diagnosing this disease a study of the protein polycystin-1 which when mutated is responsible for polycystic kidney disease, will be analysed by using proteomic methods. Firstly, the polycystin-1 protein must be extracted from a patient who wishes to obtain diagnosis of the disease. Since polycystin-1 is a membrane protein and is located in the kidney it will be necessary to extract kidney tissue from the patient by carrying out a quick and simple biopsy procedure. The biopsy removes kidney tissue by inserting a thin biopsy needle through the skin and into the kidney whilst the patient is under local anaesthetic. Now that tissue containing the polycystin-1 or its mutated form is extracted from the patient it must be treated in order to release the proteins contained within the tissue. The tissue will firstly be homogenized and lysed in order to release the proteins into solution. The sample will then be centrifuged at 14,000 rpm at 4ÃÅ'Ã…  C for 15 min. This centrifugation step removes any insoluble material and the supernatant will contain the proteins from the tissue sample including the protein of interest polycystin-1. This method was carried out by Malhas, Abuknesha, and Price 2001 whilst trying to crystalize the polycystin-1 protein. Now that polycystin-1 is in solution it can be separated from the other proteins by means of 2D gel electrophoresis. This technique will separate the polycystin-1 protein from other proteins based firstly on their isoelectric points (pIs) and secondly by their molecular weight. After carrying out this two-dimensional separation the gel is stained with stains such as coomassie brilliant blue (CBB) or silver staining in order to visualize the spots on the gel. By carrying out bioinformatical analysis the molecular weight and pI of polycystin-1 can easily be obtained (Mishra 2010). The molecular weight of polycystin-1 is 460.3 kDa and it has a pI of 6.27. With this information, the band which corresponds to the molecular weight and pI of polycystin-1 can be easily identified and excised from the gel. Before excising the polycystin-1 protein from the gel it must first be fragmented into peptides using trypsin cleavage. By fragmenting the protein with trypsin, peptide molecules are formed which are now suitable to be sequenced using MALDI-TOF mass spectrometry. These peptides must then be suspended in a matrix suitable for MALDI-TOF MS. An example of such a matrix is ÃŽÂ ±-cyano-4-hydroxycinnamic acid which was used in the work carried out by Malhas, Abuknesha, and Price, when they crystallized the polycystin-1 protein using the MALDI-TOF technique. This matrix is suitable as the peptides are below 5 kDa. The matrix and peptide mixture is then loaded onto the metal plate of the MALDI-TOF MS analyser where it will be hit by a pulsing UV laser. The matrix molecules absorb the UV light causing the matrix molecules to enter the gas phase along with their coupled vaporised peptides which then become ionized. The TOF MS then measures the time it takes the ions to fly as lighter ions travel faster. The ions will then hit the ion detector and the on board computer will produce the plot of the mass spectrum (Kraj and Silberring 2008). MALDI-TOF MS is the ideal method to analyse the polycystin-1 protein as like ESI, it is a soft ionization technique meaning there will be little or no fragmentation of the compounds being analysed. Once the mass spectrum is obtained it is then compared to the mass spectrum of the normally functioning polycystin-1 protein which can theoretically be fragmented by trypsin in the online databases. Any differences between the sample and the known mass spectrum of the normal protein will signal a mutation has occurred. This method of protein analysis is a very effective and efficient way of screening for the mutated proteins. The study carried out by Brioude et al 2016 proves this as they looked at using MALDI-TOF MS to test for mutated proteins leading to lung tumours. In this study, they concluded that the method is very promising and it should be used in several surgical settings where rapid evaluation of abnormal tissue is required. This highlights how this new method of analysing polycystin-1 for a mutation could prove very effective in diagnosing polycystic kidney disease. This method holds a distinct advantage over the imaging methods currently in use as diagnosis can be made early in a patients life before they show symptoms or the formation of cyst on their kidneys which are associated with polycystic kidney disease. Early diagnosis of this disease means that drugs for the prevention of cyst formation such as Jinarc © which contains the API Tolvaptan can prolong a patients kidney function by slowing down the rate at which the fluid filled cysts on the kidneys are formed. This method is used to identify a mutation of the polycystin-1 protein which attributes to 85% of autosomal dominant polycystic kidney disease cases. The other 15% is made up of mutations of the protein polycystin-2. Fibrocystin is the mutated protein responsible for autosomal recessive polycystic kidney disease. Both the dominant and recessive forms of this disease can be diagnosed using the above method in order to identify a mutation in either polycystin-2 or fibrocystin proteins if there is no mutation of polycystin-1 observed. From the above sections, it can be seen how sever and prominent polycystic kidney disease is worldwide. Although this disease is genetically inherited from or both parents, symptoms of the disease are slow progressing. In 85% of cases the disease will not advance to renal failure until the patient is 50-60 years of age. The current diagnostic techniques currently used by doctors such as imaging and genetic testing have their benefits however they are also flawed. The major disadvantage seen in this project regarding the current diagnostic techniques is the diagnosis of polycystic kidney disease in a patient where uncontrolled cyst formation has already occurred and serious renal problems have begun. With the use of our new proteomic technique earlier diagnosis will be possible before the disease has progressed to renal failure. Early diagnosis means that the use of drugs such as Tolvaptan © can be used to significantly slow down cyst formation which will ultimately increase the length of time a patient suffering with polycystic kidney disease has before renal failure occurs. 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[online] Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/orphans/2013/09/human_orphan_001257.jspmid=WC0b01ac058001d12bsource=homeMedSearch [Accessed 4 Mar. 2017]. F. Gaillard (2015) Autosomal Recessive Polycystic Kidney Disease Radiopaedia Journal, 01(1). F.Belibi C. Edelstein (2008) Unified Ultrasonic Diagnostic Criteria for Polycystic Kidney Disease Journal of the American Society of Nephrology, 20 (1). Gallagher, A., Germino, G. and Somlo, S. (2010). Molecular Advances in Autosomal Dominant Polycystic Kidney Disease. Advances in Chronic Kidney Disease, 17(2), pp.118-130. K.Hayashi (1991) PCR-SSCP: A Simple and Sensitive Method for Detection of Mutations in the Genomic DNA Genome Research, 01 (1). Kraj, A. and Silberring, J. (eds.) (2008) Proteomics: Introduction to methods and applications. Chichester, United Kingdom: John Wiley Sons. MacDermot, K., Saggar-Malik, A., Economides, D. and Jeffery, S. (1998). 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Prophylactic Internal Iliac Artery Ligation Health Essay

Aim: to measure the function of internal iliac arteria ligation as an effectual method of commanding station partum bleeding due to sidelong uterine rupture. Subjects and methods: A randomized controlled survey was conducted on 50 pregnant adult females who were admitted to Shatby University Maternity Hospital between June 2006 and August 2008, all of them were diagnosed as station partum bleeding due to sidelong uterine rupture. The patients were indiscriminately allocated to 2 groups, the ligation group where ligation of internal iliac arteria followed by fix of ruptured uterine wall was done ( group A ) , and the fix group, where ruptured womb was repaired by conventional methods ( group B ) . Informed consent was taken from all patients. Consequences: The ligation group showed a important statistical difference when compared with the fix group sing intra-operative clip ; sum of blood transfused intra-operatively ; continuance of intensive attention unit stay, need for extra surgical intervention such as hysterectomy or extra vaginal hemostasis, and the incidence of complications as disseminated intravascular coagulopathy, and ureteric hurt. Decision ; internal iliac arteria ligation is considered an alternate effectual method to hysterectomy in instances of sidelong uterine rupture, taking to diminish maternal morbidity. Cardinal words: postpartum bleeding ( PPH ) , uterine rupture, internal iliac arteria ligation ( IIAL ) , hysterectomy.IntroductionPost partum bleeding ( PPH ) is a major cause of world-wide mortality runing from 13 % in developed states to 34 % in developing states. ( 1 ) it is responsible for over 125,000 maternal deceases each twelvemonth and is associated with morbidity in 20 million adult females per twelvemonth. ( 2 ) Traditionally, PPH is defined as hemorrhage from the venereal piece of land of 500 milliliter or more in the first 24 hr following bringing of the babe, a significant autumn in the hematocrit or the demand of blood transfusion have besides been proposed. ( 2-5 ) Uterine atonicity is the common cause of PPH that accounts for 80 % of instances ; other causes include maintained placental fragments, lower venereal piece of land lacerations and uterine rupture. ( 6 ) Uterine rupture is a ruinous obstetric complication. Although an uncommon event, it continues to be associated with a high rate of perinatal and maternal morbidity and mortality. ( 7 ) The chief hazard factor for uterine rupture is a scarred womb, normally secondary to a anterior cesarean bringing. Consequently, most of the recent reappraisals on uterine rupture have focused on adult females trying vaginal birth after old cesarean bringing ( VBAC ) . ( 8 ) Rupture of the unscarred womb is a rare obstetric complication, with an estimated incidence of 1 in 8000-15,000 bringings. ( 9 ) There are two types of uterine rupture, complete and uncomplete, distinguished by whether or non the serous coat of the womb is involved. ( 10 ) In the former the uterine contents including foetus and on occasion placenta, may be discharged into the peritoneal pit, whereas in the latter the serous coat is integral and foetus and placenta are inside the uterine pit. ( 11 ) The complete assortment appears to be more unsafe of the two assortments. ( 12 ) Rupture of womb during labour is more unsafe than that happening in gestation because daze is greater and infection is about inevitable. ( 13,14 ) When PPH continues despite aggressive medical intervention, early consideration should be given to surgical intercession. The pick of process will depend on the para of the adult females and her desire for childbirth, the extent of bleeding and, most significantly, the experience and opinion of the sawbones. In most ruinous state of affairss, hysterectomy is preferred in order to collar farther blood loss and via media with certainty. ( 15 ) Although a life-saving process, it may non be appropriate for adult females who need to continue their generative potency. Haemostatic processs that preserve the uterus include uterine pit tamponage, selective uterine arteria embolisation, uterine arteria ligation and uterine brace suturas. ( 16 ) ISSN 1110-0834Internal iliac arteria ligation ( IIAL ) for the control of profuse pelvic hemorrhage has long been recognized as a life-saving process. ( 17 ) The American College of Obstetricians and Gynaecologists continues to recommend the usage of hypogastric arteria ligation in the direction of intraoperative intractable bleeding during pelvic surgery or in instances of obstetric bleeding. ( 18 ) The construct that surcease of blood supply may do harm to pelvic variety meats has been proved to be incorrect. On the contrary, in the instance of pelvic bleeding unmanageable by conservative methods, prompt intercession may non merely salvage the life of the patient but besides her womb. There are several studies of gestations carried to full term after bilateral ligation of the hypogastric arterias. ( 19-23 ) The purpose of this survey was to measure the function of bilateral IIAL in instances of terrible station partum bleeding due to sidelong rupture womb in comparing to the conventional uterine fix merely in such instances.MethodThis survey was conducted on 50 pregnant adult females who were admitted to Shatby University Maternity Hospital between June 2006 and August 2008, all of them were diagnosed as terrible station partum bleeding due to sidelong uterin e rupture which might be extended to the vagina ( Diagnosis was confirmed during Laparotomy ) . The sample group were indiscriminately allocated into two groups: Group A=35 patients ( ligation group ) : adult females were subjected to bilateral IIAL followed by fix of uterine wall. Group B =15 patients ( fix merely group ) : adult females were subjected to conventional methods of uterine fix. All patients were counselled for the process and informed consent was obtained.Technique of internal iliac ligation was done as follow:The womb is lifted out of the pelvic girdle in order to observe the extent of the hurt. The uterine tear is inspected and examined carefully from the vertex downwards. The hemorrhage borders of the womb are held with Green Armytage clinch ( or pealing forceps ) . The vesica is dissected from the lower uterine section by crisp and blunt dissection so mobilized downwards. The external iliac pulsings are felt and followed up to the bifurcation of the common iliac arteria, and the ureter is identified. The peritoneum on the sidelong side of the bifurcation of the common iliac arteria is opened by a longitudinal scratch in such a manner that the ureter remains attached to the median peritoneal contemplation exposing the retroperitoneal anatomy. The internal iliac arteria is traced and carefully dissected off from the underlying vena. Figure ( 1 & A ; 2 ) A dual yarn of absorbable sutura ( Vicryl ) stuff is passed underneath the arteria and tied. Figure ( 3 ) Femoral arteria pulsings are identified after binding the ligatures.Statistical methods:Statistical analysis was done utilizing Statistical Package for Social Sciences ( SPSS/version 15 ) package. The statistical trials used are as follow: Arthematic mean, standard divergence, Chui-square trial and Fisher exact trial was used for categorised parametric quantities, while for numerical informations, t-test was used. The degree of significance was 0.05.ConsequenceIn the ligation group ( group A ) , the age ranged from 24 – 39 old ages with a mean of 32.85A ±6.57 and para ranged from 1-4 with a mean of 2.45A ±1.01, while in the fix group ( group B ) their age ranged from 27-42 old ages with a mean of 33.9A ±7.06 and the para ranged from 1-4 with a mean of 2.622A ±1.05, severally. There was no statistically important difference between the two groups sing age and para. Both groups were compared as respects intra-operative and, postoperative eventsIntraoperative events:The average intra-operative clip in group ( A ) was 45.5A ±4.68 proceedingss, while it was 98.5A ±8.98 proceedingss in group ( B ) . The intra-operative clip is statistically important longer in group B as P= 0.0001. The clip needed for one- sided IIAL ranged between three to seven proceedingss. The average blood volume transfused intra-operatively in group ( A ) was 1750A ±71.6 milliliter, compared to 2980A ±120.8 milliliters in group ( B ) , this difference is statistically important as P= 0.0001. In group ( A ) , Four patients ( 11.4 % ) had hysterectomy, and 6 patients ( 17.1 % ) had extra haemostatic vaginal suturas for extended vaginal cryings after IIAL. In group ( B ) seven patients ( 46.7 % ) had hysterectomy and 10 patients ( 66.7 % ) had haemostatic vaginal suturas. These difference, are statistically important as P= 0.0058 and 0.0005 severally. These findings revealed a higher incidence of extra secondary processs in group ( B ) . There was no ureteric ligation or hurt recorded in group ( A ) , on the other manus in group ( B ) the ureter was ligated on the same side during fix of the tear without exposing the ureter in 2 instances. Fortunately, both discovered intra-operatively and managed. No other complications were recorded in either group. ( Table I )Postoperative eventsAll patients were transferred postoperatively to intensive attention unit ( ICU ) the average continuance of ICU stay was 38A ±5.99 hours in group ( A ) , compared to 70A ±6.85 hours in group B, which is statistically important as P= 0.0001. On the other manus, 5 patients ( 14.3 % ) in group ( A ) which is statistically important less compared to 9 patients ( 60.0 % ) in group ( B ) were complicated with disseminated intra vascular coagulopathy ( DIC ) . The entire volume of blood collected from intra-abdominal drain over 48 hours postoperatively was 211A ±23.85 milliliter in group ( A ) , while it was 751A ±68.98 milliliter in group ( B ) . These revealed a higher incidence of station operative complications in group B. Merely one patient ( 2.9 % ) died from pneumonic intercalation in group ( A ) , and another one ( 6.7 % ) died in group ( B ) due to monolithic hypovolemia and daze. ( Table II ) Fig. 1: Lateral uterine rupture with terrible station partum bleeding Fig. 2: Retroperitoneal anatomy demoing the great vass. Fig. 3: A dual yarn of absorbable sutura stuff is passed underneath the arteria utilizing right angled artery forceps and tied. Table I: Comparison between the two studied groups sing intra-operative events.Group Aâ€Å" n=35 †Group Bâ€Å" n=15 †Trial of significanceIntra-operative clip ( min. ) 45.5A ±4.68 98.5A ±8.98 T = 4.30 P = 0.0001* Sum of blood transfused intra-operatively ( milliliter ) 1750A ±71.6 2980A ±120.8 T = 5.21 P = 0.0001* Need for hysterectomy 4 ( 11.4 % ) 7 ( 46.7 % ) X2 = 7.60 P = 0.0058* Need for extra vaginal haemostatic suturas 6 ( 17.1 % ) 10 ( 66.7 % ) X2 = 11.83 P = 0.0005* Ureteric ligation 0 ( 0.0 % ) 2 ( 13.3 % ) Field-effect transistor P = 0.085 Datas are presented as Mean + SD * P is important if & lt ; 0.05 Field-effect transistor: Fisher Exact ‘s Trial Table II: Comparison between the two studied groups sing post-operative events.Group Aâ€Å" n=35 †Group Bâ€Å" n=15 †Trial of significanceDuration of ICU stay in hours 38A ±5.99 70A ±6.85 T = 4.25 P = 0.001* Incidence of DIC 5 ( 14.3 % ) 9 ( 60.0 % ) X2 = 10.88 P = 0.0009* Entire sum of blood collected in drain over 48 hours ( milliliter ) 211A ±23.85 751A ±68.98 T = 6.21 P = 0.0001* Maternal mortality 1 ( 2.9 % ) 1 ( 6.7 % ) Field-effect transistor P = 0.524 Datas are presented as Mean + SD * P is important if & lt ; 0.05 Field-effect transistor: Fisher Exact ‘s Test DIC: disseminated intra vascular coagulopathy Intensive care unit: intensive attention unitDiscussionUterine rupture is a serious obstetric complication, with high morbidity and mortality, peculiarly in less and least developed states. The most of import defect of the information available is the deficiency of distinction between uterine rupture with and without old cesarean subdivision. Overall, most rates ranged between 0.1 % and 1 % . Maternal mortality ranged between 1 % and 13 % , and perinatal mortality between 74 % and 92 % . ( 24 ) Uterine artery ligation is a promising technique in the direction of PPH as occlusion of the uterine arteria reduces 90 % of the blood flow. It is utile in uterine atonicity, but in uterine injury, when the avulsed uterine arteria retracts into the wide ligament organizing a hematoma, it is hard to make a uterine arteria ligation and salve the womb. IIAL in such state of affairss is helpful as the force per unit area and flow of circulation lessening distal to the ligation and enabling one to readily turn up the hemophiliac and ligate it firmly. Similarly, in instances of deep forniceal cryings and hematoma, uterine arteria ligation or even hysterectomy does non halt the bleeding. In such instances, blood loss could be arrested after IIAL as vaginal arteria is a direct subdivision of anterior division of internal iliac arteria. Since it is a safe, rapid and really effectual method of commanding shed blooding from venereal piece of land, it is besides helpful in commanding postoperative bleeding after abdominal or vaginal hysterectomy where no unequivocal hemorrhage point is noticeable. IIAL was performed for the first clip by Kelly ( 25 ) with a success rate 95 % and without any major complication. Mukherjee et Al ( 26 ) performed 36 instances of IIAL with a success rate of 83.3 % in 6 old ages. The principle for IIAL as an effectual agencies of commanding intractable PPH and forestalling maternal decease is based on the haemodynamic surveies of Burchell, ( 27 ) which showed that IIAL reduced pelvic blood flow by 49 % and pulse force per unit area by 85 % , ensuing in venous force per unit areas in the arterial circuit therefore advancing hemostasis by a simple coagulum formation. However, the reported success rate of IIAL varies from 40 to 100 % , ( 28 ) and the process averts hysterectomy in merely 50 % of instances. ( 29 ) Papp et Al, ( 30 ) published aA reappraisal of indicants and results for 117 instances of bilateral hypogastric arteria ligation over 15 old ages ( 1990-2004 ) . They documented that, apart from a little lesion to the hypogastric vena, no complications were observed. Bleeding was efficaciously controlled in all 37 obstetric instances. In 13 of these instances, the womb was preserved even when there was cervical gestation, placenta previa, placental breaking off, uterine atonicity, and uterine rupture, and 4 adult females were delivered of mature babies. Bleeding was efficaciously controlled in 41 of 80 gynaecological instances. Contraceptive decrease of pelvic blood flow was the indicant for the process in 39 cases.The womb was preserved in merely a few of the 41 controlled instances, but one adult female ( so far ) was delivered of a mature baby. In our survey we evaluated the efficaciousness of ligation of internal iliac arteria in instances of rupture womb. Results showed less operative clip and sum of blood transfused for replacing in comparing to the fix group. In add-on, the womb was preserved in most of the instances, merely 4 patients ( 11.4 % ) had hysterectomy, and 6 patients ( 17.1 % ) had extra vaginal suturas for hemostasis. There were no ureteric or great vessel hurts. The post-operative events, showed short ICU stay and less incidence of complications as DIC was merely seen in 5 patients ( 14.3 % ) , besides it is fertility salvaging process. The fright of vascular hurt and return of bleeding normally deter an obstetrician from fall backing to IIAL. We observed that one time the uterine hemorrhage was controlled during surgery, it did non repeat in the postoperative period in any adult female in whom the womb was conserved. As there is free inosculation providing pelvic variety meats, vascular lack following ligature have non proved to be a job, even after bilateral IIAL. Khelifi et Al. ( 31 ) have evaluated internal iliac arterias in 13 adult females after ligation by color Doppler echography in the 4th twenty-four hours after intercession and so monthly until repermeabilization of the internal iliac arterias. In all instances, the first test showed down-side the ligature, a flow inversion with an of import pelvic indirect circulation. The following Doppler test showed repermeabilization of the hypogastric arterias after an mean interval of 5 months. Pappz et Al. ( 21 ) have reported a successful gestation after internal iliac arteria ligation with normal flow speed in uterine arterias. Wagaarachchi and Fernando ( 22 ) observed successful gestation in 50 % of the instances following bilateral ligation. Therefore, Internal iliac arteria ligation decreases the hemorrhage, clears the operative field and therefore enables the sawbones to avoid blindly clamping and ligating tissues submerged in a pool of blood. This is peculiarly helpful in cut downing the hazard of ureteric hurt. Internal iliac arteria ligation besides facilitates fix of vaginal lacerations that bleed abundantly with each sutura through the vaginal wall. It represents an option to the hysterectomy and preserves the child-bearing maps of some females because of the subsequent vascular recanalization. All accoucheurs caring for parturient adult females should familiarise themselves with this process as it should be an built-in portion of obstetric and gynaecological preparation.

The Dos and Donts of Tasc Writing Argumentative Essay Samples

The Do's and Don'ts of Tasc Writing Argumentative Essay Samples Things You Won't Like About Tasc Writing Argumentative Essay Samples and Things You Will The rest of your essay is subsequently devoted to proving this claim. Frequently the discussions become heated up as debates and wind up as arguments. You're going to need to choose a topic first, but your topic ought to be something that has two conflicting points or distinct conclusions. Write down possible suggestions to utilize for the key arguments and supporting paragraphs. Life, Death, and Tasc Writing Argumentative Essay Samples The amazing argumentative Scholarship Essay Samples formats and samples are just world-class, and they'll inspire folks to write argumentative essays in various competitions. You should inform. Want to Know More About Tasc Writing Argumentative Essay Samples? Practicing the elements of excellent essay writing is helpful regardless of what topic you concentrate on. 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Know as much as possible about your side, but know equally as much if not more regarding the opposing side too. While the focus is mostly on your side, there's also a discussion about the opposing side which goes far beyond a single sentence or a paragraph. Always bear in mind that you're not just arguing about your stand but in addition counter the potential stand of the opposing viewpoint. One of the greatest things you can do in order to be sure you're prepared to take the Praxis writing test is to practice writing essays. Logic is another feature of a great argumentative essay which you should consider when searching for examples to refer to. In order to get this done, you ought to be know ledgeable about some of the characteristics of an argumentative essay. The upcoming few paragraphs will constitute most of your essay. It is an entire outline of the way to prepare an argumentative essay for college. But most essay examples are readily available to students at no cost. Reviewing essay examples can help you learn to compose a high-scoring essay. All three of the main HSE tests provide sample prompts and passages. If at all possible, your test prep should include things like essays scored by means of an instructor. Be certain to answer the multiple-choice questions given in the lesson quizzes and chapter tests to ensure you're prepared for test day. Before you commence studying, figure out which test is given in your state. The 5-Minute Rule for Tasc Writing Argumentative Essay Samples Begin each paragraph by stating the principal point that you would like to speak about. This outline can be extremely helpful in regards to writing your conclusion too. Bear in mind you don't have to produce a title for your essay. After you feel confident that you fully grasp the writing prompt, utilize a sheet of paper to brainstorm your ideas. The Debate Over Tasc Writing Argumentative Essay Samples Or, you might point to studies identifying climate change as one of the best sources of tension and fear in the world population. Should you want, highlight the important words and phrases in the stimulus to have the ability to look at it from time to time to be sure you adhere to the topic. You'll give evidence from the passage in addition to from your understanding and experience. The only problem includes grammar problems like harmful rather than harm in the question at the start. Lies You've Been Told About Tasc Writing Argumentative Essay Samples A best sample needs to have a structure which represents proper assembly and integration of all of the claims of the paper for smooth stream of ideas. Before you turn in your assignment, you are going to want to appear over it one final moment. This will allow you to se e certain areas where you will need improvement. This specific area can include no more than three paragraphs to as many as necessary to finish your assignment requirements. Coal is utilized in Canada to earn electricity. The process that's utilized to select the oil from the sand also pollutes the air. You should know example, when submitting an application for work, you will need to write about your prior experience. This formal argumentative example can help you exactly in this field. Bear in mind an argumentative essay is based more on facts instead of emotion. The thing you ought to do as a way to structure an argumentative essay is to set a claim that's debatable. It presents both sides of an issue. It is a type of essay that presents arguments about both sides of an issue. The One Thing to Do for Tasc Writing Argumentative Essay Samples You begin by asking a question, which is a great way to begin. It provides you a lot of ideas which will help you form your essay easily. Lots of people find writing as an effective means to share their thoughts and opinions. Likewise, it has to be logically complete and express a particular idea.

The Effect Of Metoprolol On The World Health Organization...

METOPROLOL Introduction Metoprolol is a selective ÃŽ ²1 receptor blocker.1 It is used to treat high blood pressure or hypertension, myocardial infarction (MI), heart failure and angina pectoris.2 Metoprolol was first made in 1969 and is on the World Health Organization’s list of essential medicines.3 Metoprolol is available only in its salt form due to its low melting point, such as metoprolol tartrate or metoprolol succinate. Its salt form, metoprolol tartrate was first developed by Novartis and was approved by FDA on August 7, 1978.4 Metoprolol is also available as a generic drug.1 Drug Profile Figure 1. Chemical Structure of Metoprolol IUPAC Name : 1-(isopropylamino)-3-[4-(2-methoxyethyl)phenoxy] propan-2-ol Chemical Formula : C15H25NO3 Molecular Weight : 267.364 g/mol Trade names : Lopressor, Metolar XR, Toprol XL (US) Nature : Free base exists as a white solid, while its tartrate form exists a fine crystalline material.5 Physical properties* : Solubility – Very soluble (water), Freely soluble (methylene chloride, chloroform, alcohol), Slightly soluble (acetone) and Insoluble (ether).6 Melting point - 120 °C or 248 °F.5 *Properties are given, considering the salt form, metoprolol tartrate. Pregnancy category : C (US). Indicates that it’s a risk when used during pregnancy. Route of administration : Oral and Intravenous (IV) Pharmacokinetic data : Bioavailability – 50%7 Protein binding – 12% Metabolism – Liver via CYP2D6, CYP3A4 Half-Life – 3-7 hoursShow MoreRelatedSelf Medication Practices in a Rural Filipino Community21296 Words   |  86 PagesUNIVERSITY OF SAINT LOUIS TUGUEGARAO TUGUEGARAO CITY, CAGAYAN College Of Health and Allied Sciences Master Of Science In Nursing Major In Adult Health Nursing In fulfillment of the Requirement for the Degree Master of Science in Nursing Major in Adult Health Nursing Factors Affecting The Prevalence Of Self Medication Using Commercial Drugs In A Rural Filipino Family For The Course Research II With Statistics Presented by: Elaiza Joy M. Claravall Hazel Faith W. Cortel Read MorePharmaceutical Price Controls in the Oecd Countries47662 Words   |  191 Pages22161; www.ntis.gov. ii U.S. Department of Commerce, International Trade Administration Contents Executive Summary vii 1 Introduction 1 2 Drug Price Regulations in Selected OECD Countries—An Overview of the Issues 3 3 Price And Revenue Effects 10 4 Impact of Deregulating Prices on Research and Development, Innovation, and Consumers 25 Appendix A: Technical Methodology 35 Appendix B: Drug Pricing Study—Federal Register Notice Responses 49 Appendix C: Report on Pharmaceutical Markets in 11Read MoreThe Marketing Research of Brainquiry33782 Words   |  136 Pagestools and how much they would budget for that. The German research gives an overview of a sample of contact details of doctors divided into users and non users of neuro/biofeedback. This information is to be found on the CD in the folder Germany. A list of contact details for golf clubs throughout Germany is given in the same excel file as mentioned before. If more contacts are needed they can be found by using the means stated in the sources part of the research. The excel file gives furthermoreRead MoreComprehensive 1 Essay18452 Words   |  74 Pagestransmitted by the bite of an infected deer tick, and antiviral agents (D) are ineffective. Symptoms, such as fever, chills, headache, stiff neck, fatigue, and swollen lymph nodes are more typical, not nausea and vomiting (C).   Category:   Community Health Awarded 1.0 points out of 1.0 possible points. 2. 2.ID: 310982379 The nurse is planning a wellness program aimed at primary prevention in the community. Which action should the nurse implement? A.   Immunizations that decrease occurrences of many contagious